Chemoprevention of basal cell carcinoma with vitamin D

描述（由申请人提供）：这是一份美国加州大学旧金山分校皮肤科医生Jean Tang博士的K23奖申请。唐博士是一名以患者为导向的基底细胞癌（BCC）预防转化研究的年轻研究者。该K23奖将为唐博士提供必要的支持，以实现以下目标：(1)开展维生素D预防BCC的小鼠临床前试验；(2)对具有维生素D基线测量值的大型前瞻性老年男性队列进行二次数据分析；(3)进行人体试验，以测试外用或口服维生素D3的可行性。为了实现这些目标，唐博士组建了一个指导团队，其中包括一位主要导师，奥克兰研究所儿童医院的科学家Ervin Epstein博士，他在BCC的化学预防方面进行实验室和临床试验，以及三位共同导师：旧金山协调中心主任Steven Cummings博士，他是临床研究和大型患者队列试验方面的专家；皮肤科结果研究专家Mary-Margaret Chren博士；查尔斯·麦卡洛博士是纵向数据分析和生物统计学方面的专家。目前，尚无有效的预防基底细胞癌（BCC）的药物。防晒霜并没有被证明可以预防基底细胞癌；然而，最近的体外数据表明，维生素D3抑制BCC中发现的异常信号通路。唐博士已经证明，局部应用维生素D3可以预防50%的bcc。在这项研究中，她建议确定维生素D3抑制小鼠BCC的最佳途径（目的1），并确定高水平的血清维生素D是否能降低老年男性BCC的风险（目的2）。唐医生还将进行一项试点临床试验，以测试患有多发性基底细胞痣综合征的患者局部和口服维生素D3的可行性（目标3）。我们将从小鼠临床前试验和人体先导试验中确定维生素的最佳给药方案

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Jean Tang, a dermatologist at the University of California, San Francisco. Dr. Tang is establishing herself as a young investigator in patient-oriented, translational research in the prevention of basal cell carcinoma (BCC). This K23 award will provide Dr. Tang with the support necessary to accomplish the following goals: (1) to conduct a mouse preclinical trial on vitamin D for BCC prevention; (2) to conduct secondary data analysis in a large prospective cohort of senior men that have baseline vitamin D measurements; (3) to conduct a pilot clinical trial in humans to test the feasibility of topical or oral vitamin D3. To achieve these goals, Dr. Tang has assembled a mentoring team comprised of a primary mentor, Dr. Ervin Epstein, Scientist at Children's Hospital of Oakland Research Institute, who conducts laboratory and clinical trials in chemoprevention of BCC, and three co-mentors: Dr. Steven Cummings, Director of the San Francisco Coordinating Center who is an expert in clinical studies and trials of large patient cohorts; Dr. Mary-Margaret Chren, an expert in dermatology outcomes research; and Dr. Charles McCullough, who has expertise in longitudinal data analysis and biostatistics. Currently, there is no effective agent to prevent basal cell carcinomas (BCC). Sunscreens have not been shown to prevent BCC; however, recent in vitro data suggests that vitamin D3 inhibits the aberrant signaling pathway found in BCC. Dr. Tang has shown that topical application of vitamin D3 in mice will prevent 50% of BCCs. In this K23, she proposes to determine the optimal route of delivery of vitamin D3 for inhibition of BCC in mice (Aim 1) and to determine whether high levels of serum vitamin D reduce BCC risk in senior men (Aim 2). Dr. Tang will also conduct a pilot clinical trial to test the feasibility of topical and oral vitamin D3 in patients with basal cell nevus syndrome who have multiple BCCs (Aim 3). From the mouse preclinical trial and the human pilot trial, we will determine the optimal administration of vitamin D3 for inhibition of a biomarker of BCC. These results will provide critical preliminary data for a randomized controlled clinical trial using vitamin D3 for prevention of BCC tumors in Basal Cell Nevus Syndrome patients, which will be developed during the K award and submitted as a R34 grant application to the NIH at the end of Year 5. RELEVANCE (See instructions): Sunscreens do not prevent basal cell carcinomas of the skin, the most common cancer found in the US. Our goal is to determine whether vitamin D is an effective and safe agent to prevent basal cell carcinomas.